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在肝星细胞中的PFKFB3介导的糖解促进肝脏再生

Yapeng Cao¹, Siyu Wang¹, Min Zhang¹

¹Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Xi'an, 710061, China.

Biochemical and biophysical research communications

|April 19, 2024

概括

激活的肝星细胞 (HSC) 通过PFKFB3增强糖解,这对肝脏再生至关重要. 使用PFKFB3抑制剂准这种途径显著阻碍了LR,突出了PFKFB3的作用.

科学领域:

肝病学肝病学是一种肝病学.
细胞的新陈代谢
分子生物学分子生物学

背景情况:

肝星细胞 (HSC) 是肝脏再生 (LR) 的关键参与者.
糖解调节对于LR期间的细胞增殖至关重要.
PFKFB3是糖解的重要调节剂.

研究的目的:

为了调查激活的高酸盐是否通过PFKFB3.3增强糖解.
为了确定是否针对PFKFB3途径有利于LR.
阐明PFKFB3在HSC介导的肝细胞增殖中的作用.

主要方法:

定量RT-PCR和西式斑点测试用于评估小鼠肝脏和部分肝切除术 (PHx) 后的HSC中的PFKFB3表达.
在初级HSC中测量糖解水平.
在体外研究中使用人类LX2细胞与PFKFB3敲击和PFKFB3抑制剂3PO.
评估肝细胞增殖和MAPK信号通路 (p38和ERK1/2) 对PFKFB3调制的反应.

主要成果:

在PHx后的HSC中,PFKFB3表达和糖解水平显著增加.
在LX2细胞中减少了PDGF诱导的糖解增强.
给予PFKFB3抑制剂3PO几乎完全阻止了PHx小鼠的肝细胞增殖.
抑制PFKFB3降低了LO2细胞和孤立肝细胞中的p38和ERK1/2酸化和增殖.

结论:

在HSC中PFKFB3的激活对于PHx后的肝脏再生至关重要.
PFKFB3增强糖解和乳酸生产,促进肝细胞的增殖.
向PFKFB3代表了肝脏再生的潜在治疗策略.

关键词:

肝脏的星状细胞是什么肝细胞的增殖肝细胞的增殖乳酸盐是一种乳酸盐.肝脏的再生再生 PFKFB3B3 是一个很好的选择.

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